Epigenome-Wide Meta-Analysis of Methylation in Children Related to Prenatal NO2 Air Pollution Exposure

Prenatal exposure to air pollution is considered to be associated with adverse effects on child health. This may partly be mediated by mechanisms related to DNA methylation. In this study, the authors investigated associations between exposure to air pollution, using nitrogen dioxide (NO2) as marker, and epigenome-wide cord blood DNA methylation. The associations between NO2 exposure at residential addresses during pregnancy and cord blood DNA methylation (Illumina 450K) in four European and North-American studies (n=1,508) were meta-analysed with subsequent look-up analyses in children aged 4 (n=733) and 8 (n=786) years. Additionally, a literature-based candidate approach for antioxidant and anti-inflammatory genes was applied. To assess influence of exposure at the transcriptomics level, the authors related mRNA expression in blood cells to NO2 exposure in 4- (n=111) and 16-year-olds (n=239). Epigenome-wide significant associations (false discovery rate (FDR) p<0.05) between maternal NO2 exposure during pregnancy and DNA methylation in newborns was found for 3 CpG sites in mitochondria-related genes: cg12283362 (LONP1), cg24172570 (3.8 kbp upstream of HIBADH), and cg08973675 (SLC25A28). The associations with cg08973675 methylation were also significant in the older children. Further analysis of antioxidant and anti-inflammatory genes revealed differentially methylated CpGs in CAT and TPO in newborns (FDR p<0.05). NO2 exposure at the time of biosampling in childhood had significant impact on CAT and TPO expression. The authors concluded that NO2 exposure during pregnancy was associated with differential offspring DNA methylation in mitochondria-related genes. Exposure to NO2 was also linked to differential methylation as well as expression of genes involved in antioxidant defence pathways. Authors: Gruzieva O, Xu CJ, Breton CV, Annesi-Maesano I, Antó JM, Auffray C, Ballereau S, Bellander T, Bousquet J, Bustamante M, Charles MA, de Kluizenaar Y, den Dekker HT, Duijts L, Felix JF, Gehring U, Guxens M, Jaddoe VV, Jankipersadsing SA, Merid SK, Kere J, Kumar A, Lemonnier N, Lepeule J, Nystad W, Page CM, Panasevich S, Postma D, Slama R, Sunyer J, Söderhäll C, Yao J, London SJ, Pershagen G, Koppelman GH, Melén E. ;Full Source: Environmental Health Perspectives. 2016 Jul 22. [Epub ahead of print] ;